Systems and methods for endotracheal delivery of frozen particles

ABSTRACT

A treatment system delivers a breathing gas and frozen ice or other particles (FSP) to a bronchus of a lung of a patient in order to induce hypothermia. The breathing gas and the FSP are usually delivered through separate lumens. Clogging of an FSP lumen can be inhibited by heating and/or cooling of the lumen. The temperature of exhaled gases or a body temperature may be measured, and a controller can adjust the duration or rate at which the ice particles are delivered in order to control the patient&#39;s core temperature based on the measured temperature.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/575,306 (Attorney Docket No. 32138-707.831), filed Nov. 17, 2017,which is a National Stage Entry of PCT/US2016/019202 (Attorney DocketNo. 32138-707.601), filed Feb. 23, 2016, which claims the benefit ofprovisional application No. 62/119,711 (Attorney Docket No.32138-707.102), filed on Feb. 23, 2015, of provisional application No.62/131,773 (Attorney Docket No. 32138-708.101), filed on Mar. 11, 2015,of provisional application No. 62/246,306 (Attorney Docket No.32138-709.101), filed on Oct. 26, 2015, and of provisional applicationNo. 62/277,412 (Attorney Docket No. 32138-711.101), filed on Jan. 11,2016, the full disclosures of which are incorporated herein byreference.

BACKGROUND OF THE INVENTION 1. Field of the Invention

The following inventions relate generally to apparatus and methods forselective modification and control of a patient's body temperature.Specifically, the inventions relate to systems and methods for loweringa patient's body temperature by heat exchange effected through thepatient's lungs.

The respiratory system provides a pathway for rapid induction oftherapeutic hypothermia through enhanced heat exchange with media orgases introduced into the lungs. The following inventions are useful forinducing therapeutic hypothermia for treating a variety of conditions,including but not limited to, acute myocardial infarction and stroke.Simple methods for inducing hypothermia are known in the art includingmethod like wrapping the patient in cooling blankets, invasiveintravascular blood cooling catheter, simple extracorporeal packing ofthe patient with ice, infusion of cold saline, etc. However, all thesemethods suffer from the lack of speed at which hypothermic temperaturescan be achieved for the patient.

2. Description of the Background Art

The following commonly owned U.S. Patents and U.S. Patent Publicationrelate to hypothermia induced through heat exchange with a patent'slungs: U.S. Pat. Nos. 8,402,968; 8,281,786; 8,100,123; 2012/0167878;20140060534; and 2015/0068525, the full disclosures of which areincorporated herein by reference.

BRIEF SUMMARY OF THE INVENTION

The embodiments described below provide improvements over existinginduced hypothermia approaches by introducing a respiratory gasconcurrently with frozen particles, typically comprising saline, water,or another aqueous solution, often in the form of a frozen mist, intothe lungs to thereby enhance the heat exchange with the patient andsubsequently enhance the speed of therapeutic hypothermia induction.

The present invention provides methods for lowering a core bodytemperature of a patient. The methods comprise delivering a breathinggas and frozen particles (FSP) to a trachea or a bronchus of a lung ofthe patient, typically during a series of inhalation cycles. Thepatient's respiratory system includes the lungs, the trachea, the nasalsinuses and nasal passages, and the lung comprises a main bronchus whichdivides into a right bronchus and a left bronchus which in turn branchinto smaller secondary and tertiary bronchi still further branch intosmaller tubes, known as bronchioles. In the specific embodiments, theFSP will be released into the trachea or the main bronchi and will becarried into the left and right bronchi and beyond as the patient isventilated and/or inhales. The melting and patient cooling will takeplace as the FSP infuse and melt throughout at least a portion of thebranching bronchia. In other instances, the FSP could be released in theright and/or left bronchia, for example by using a bifurcated FSP lumenwith exit ports located in each of the right and left bronchia.

In most embodiments, the breathing gas and the FSP are deliveredseparately to the target bronchus, typically though separate or isolatedlumens, during at least a portion of some of the patient'sinhalation/ventilation cycles. The FSP are usually ice, comprisingmostly or entirely water or more usually saline, but could also befrozen carbon dioxide or other non-toxic materials which can melt orsublimate to absorb body heat as a result of an enthalpy of melting orsublimation. The temperature of exhaled gases is typically measuredduring at least some exhalation cycles, and the amount of frozenparticles delivered to the patient can be adjusted in order to achieve atarget core temperature based on the measured temperature of theexhalation gases.

In many embodiments of the methods of the present invention, the FSPlumen will be manipulated to inhibit clogging during FSP delivery. Forexample, the lumen may be continuously or periodically cooled tomaintain a temperature below the FSP freezing point, typically about 0°C., to inhibit melting of the externally produced particles duringtransit through the lumen. In other instances, the lumen may becontinuously or periodically heated to provide a temperature above theFSP freezing point to melt particle agglomerations that might resultfrom melting and refreezing of the FSP during transit through the lumen.

The present invention also provides systems for lowering a core bodytemperature of a patient. The systems typically comprise at least onelumen configured to deliver an amount of FSP and a separate or isolatedlumen for delivering a breathing gas to a bronchus within the patient'srespiratory system. A temperature sensor is optionally provided tomeasure a temperature of gas being exhaled through the at least oneconduit, and a controller is configured to display exhalationtemperature and optionally to adjust the amount, duration and/or rate ofdelivery of frozen particles through the at least one conduit. Using thesystem, a target core temperature of the patient can be achieved andmaintained by manually and/or automatically adjusting the amount or rateof frozen particles delivered to the respiratory system of the patient.

In many embodiments of these systems, a temperature modification unitwill be provided to selectively heat or cool the FSP lumen to inhibitclogging during FSP delivery. For example, the lumen may be continuouslyor periodically cooled with a cooling jacket and/or thermoelectric(Peltier effect) cooler to maintain a temperature below the FSP freezingpoint, typically about 0° C., to inhibit melting of the externallyproduced particles during transit through the lumen. In other instances,the lumen may be continuously or periodically heated using a heatingwire or similar heating element disposed in or over at least a portionof the length (and usually all of the length) of the FSP lumen toprovide a temperature above the FSP freezing point to melt particleagglomerations that might result from melting and refreezing of the FSPduring transit through the lumen.

In a first aspect, the present invention provides methods for lowering acore body temperature of a patient. A breathing gas is delivered to atrachea or bronchus of a lung of the patient through a breathing lumen.Frozen particles (FSP) from the FSP source are also delivered to thelung bronchus through an FSP lumen separate from the breathing lumen.The FSP exit the FSP lumen into the bronchus and are dispersed in thebreathing gas within the bronchus. The dispersed FSP melt in the lungand lung bronchus to lower the core body temperature of the patient,providing a desired degree of hypothermia. The breathing gas istypically delivered during at least a portion of at least some of thepatient's inhalation cycles that but not during any portion of thepatient's exhalation cycles. The FSP source will typically be externalto the patient, and delivering FSP to the bronchus usually comprisesdelivering pre-formed FSP from the FSP source.

These methods may further comprise inhibiting occlusion or clogging ofthe FSP lumen during delivery of the FSP. For example, clogginginhibition may comprise heating the FSP lumen during at least a portionof the FSP delivery cycle. Alternatively, inhibiting clogging maycomprise cooling the FSP lumen during at least a portion of the FSPdelivery cycle to prevent the FSP from melting. In some instances,inhibiting clogging may comprise a combination of both heating andcooling the FSP lumen, typically at different times during the deliverycycle and/or between inhalation cycles. In still other embodiments,inhibiting clogging may comprise inhibiting the flow of exhalation gasesfrom the patient back into the FSP lumen.

Inhibiting backflow of the exhalation gases from the patient into theFSP lumen may be done in several ways. First, a one-way flow valve maybe placed at or near the distal end of the FSP lumen, thus preventingmoisture-laden exhalation gases from entering the upstream end of theFSP lumen. Alternatively or additionally, a blocking valve may beprovided further downstream in the FSP lumen, typically lying externalto the patient so that the blocking valve can be accessed during atreatment protocol. Such external blocking valves may also comprise aone-way valve, but will more typically be an on-off valve which can becontrolled using a control system, as described in more detail below.

In other specific embodiments of these methods, a flowing volume ofcarrier gas which is directed a bolus of FSP to entrain the FSP in theflowing carrier gas to produce an FSP-entrained flowing carrier gasstream. In such instances, a portion of the carrier gas may be ventedfrom the FSP-entrained flowing carrier gas stream to produce agas-reduced FSP-entrained flowing carrier gas stream. The gas-reducedFSP-entrained flowing carrier gas stream is then delivered to thepatient through the FSP lumen. In this way, the amount of breathing gasin the carrier gas stream may be reduced, allowing the amount of gasdelivered in the ventilation or breathing gas stream to the patient tobe increased, which in turn provides more options for controllingventilation of the patient.

In all embodiments, it may be desirable that at least some of thesurfaces of the FSP lumen and/or other delivery components between theFSP source and FSP lumen are treated or coated to inhibit freezing ofmoisture and/or clogging of the lumens.

In a second aspect, the present invention provides methods for loweringa core body temperature of a patient. A plurality of FSP boluses isdispersed into a flowing carrier gas to entrain the FSP in the flowingcarrier gas to produce an FSP-entrained flowing carrier gas stream. TheFSP-entrained flowing carrier gas stream is delivered to a lung of thepatient simultaneously with the separate gas stream and also insynchrony with the patient's inhalation cycle. The amount of FSP in theindividual boluses and/or the rate of the inhalation cycles may beadjusted to control a rate of cooling of the patient.

In specific embodiments, a single bolus of the FSP may be delivered witheach patient inhalation, wherein the rate of cooling is controlled byadjusting the inhalation rate delivered by a ventilator. In otherembodiments, the rate of cooling may be further controlled by adjustingthe amount of FSP in said individual boluses. Still other embodiments,the rate of cooling may be controlled entirely and solely by adjustingthe amount of FSP in the individual boluses.

In these methods, a tidal volume of breathing gas is delivered to thepatient and comprises a sum of a breathing gas volume and a carrier gasvolume delivered on each inhalation cycle. The tidal volume of thebreathing gas delivered to the patient may be adjusted to a target levelby venting a portion of the carrier gas from the FSP-entrained flowingcarrier gas stream after dispersing the FSP therein and beforedelivering the FSP-entrained flowing carrier gas stream together withthe separate breathing gas stream to the lung of the patient to producea reduced FSP-entrained flowing carrier gas stream. The target tidalvolume of total breathing gas (from both the breathing gas stream andthe particle dispersion gas stream) is typically in the range from 150ml to 1000 ml, usually from 250 ml to 750 ml, per inhalation cycle. Insuch cases, typically at least 50% of gas originally present in theFSP-entrained flowing carrier gas stream is vented to produce the gasreduced FSP-entrained flowing carrier gas stream.

In a third aspect, the present invention provides systems for lowering acore body temperature of a patient. Such systems are typicallyconfigured to be used in combination within an external ventilator whichdelivers a breathing cast to a bronchus of a lung of a patient. Thesystems usually comprise a tubular device configured for advancementthrough the patient's trachea to the bronchus where the device has abreathing lumen and an FSP lumen isolated from the breathing lumen. Anexternal FSP source is configured to deliver FSP to the FSP lumen of thetubular device, and a controller is configured to adjust the amount orweight of delivery of FSP from the FSP source through the FSP lumen.Thus, a target core temperature of the patient can be achieved andmaintained by adjusting the amount or rate of FSP delivery.

In specific embodiments, the system may include a sensor configured tomeasure a temperature of an exhale gas or body temperature. Thecontroller can receive the measured temperature and adjust the amount orrate of delivery of FSP through the FSP lumen in response to changes inthe measured temperature. Usually, the controller is configured toautomatically control the delivery amount or rate of FSP in response tothe measured temperature according to a feedback control algorithm. Instill other embodiments, the controller may be configured to allow auser to manually control the delivery amount or rate of FSP delivery inresponse to the measured temperature.

These systems may be further modified to inhibit clogging of the FSPlumen resulting from melting and refreezing of FSP in the FSP lumen. Forexample, a heater may be provided to heat the FSP to inhibit clogging ofthe FSP lumen resulting from melting and refreezing of the FSP. Inparticular, the heater may comprise electrical tracing or coilspositioned over at least a portion of the FSP lumen. In otherembodiments, the systems may provide a cooler, such as a cooling jacket,configured to cool the FSP lumen to inhibit melting of the FSP and thusinhibit subsequent refreezing to clog the FSP lumen.

The systems may further comprise a means for providing a bolus of FSPfrom the external FSP source and then flowing of volume of the carriergas through the bolus to entrain the FSP in flowing carrier gas toproduce and FSP-entrained flowing carrier gas stream. Such systems mayfurther include means for venting a portion of the carrier gas from theFSP-entrained flowing carrier gas stream to produce FSP-entrainedflowing carrier gas stream. The gas-reduced FSP-entrained flowingcarrier gas stream may then be delivered to the FSP lumen. Typically,the carrier gas may be vented to produce a tidal volume of totalbreathing gas delivered to the patient in a range from 150 ml to 1000ml, usually from 250 ml to 750 ml, per inhalation cycle. Often, thecontroller will be configured to invent at least 50% of the gasoriginally present in the FSP-entrained flowing carrier gas stream toproduce the reduced FSP-entrained flowing carrier gas stream.

As used herein, the phrase “tidal volume” refers to the lung volumerepresenting the normal volume of air displaced between normalinhalation and exhalation when extra effort is not applied. In ahealthy, young human adult, tidal volume is approximately 500 mL perinspiration or 6 to 8 mL/kg of body mass.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe appended claims. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 illustrates a system comprising an endotracheal tube having botha FSP lumen and a breathing gas lumen for delivering a mist of frozenparticles to a patient, as shown in parent application Ser. No.14/479,128.

FIG. 2 is a graph illustrating exemplary frozen particle deliverypatterns useful in the systems and methods of the present invention, asshown in parent application Ser. No. 14/479,128.

FIG. 3 is a schematic view of a patient interface tube (PIT) having acooling jacket incorporating some of the features of the presentinvention.

FIG. 4 is a schematic view of a patient interface tube (PIT) having aheating coil incorporating some of the features of the presentinvention.

FIGS. 5 and 5A illustrate a combined ventilator-PIT incorporating someof the features of the present invention.

FIG. 6 illustrates a combined ventilator-PIT having a movable internalseptum incorporating some of the features of the present invention.

FIGS. 7, and 7A-7C illustrate a combined ventilator-PIT having separablePIT and ventilator tube components with the components disassembled.

FIGS. 8 and 8A-8C illustrate the combined ventilator-PIT of FIGS. 7, 7Aand 7B with the components assembled.

FIGS. 9 and 9A illustrate the combined ventilator-PIT of FIGS. 7, 7A and7B connected in a system for delivery of both a breathing gas and FSP toa patient.

FIG. 10 illustrates a system for generating and controlling both an FSPstream and a breathing gas for delivery through the PIT's and ventilatortubes of the present invention.

FIG. 11 illustrates a bolt and breech assembly for injecting measuredboluses of FSP into a flowing gas stream.

FIGS. 12A-12D illustrate the step-by-step use of the bolt and breechassembly of FIG. 11 for producing the boluses of FSP.

FIGS. 13A and 13B illustrate pinch-type vent and isolation valves thatmay be disposed downstream of the bolt and breech assembly of FIG. 11for reducing the gas volume carrying the FSP and preventing back flow ofexhalation gases, respectively.

DETAILED DESCRIPTION OF THE INVENTION

System Overview: An overview of an exemplary system 10 according to thepresent invention is illustrated in FIG. 1. The systems of the presentinvention generally include a particle generator 24 which producesparticles comprising or consisting of frozen saline, water, or otherbiocompatible aqueous solution (referred to collectively hereinafter asfrozen solid particles or “FSP”); a mechanical respiration system 22;and a tubular device 12 similar to an endotracheal tube. The systems ofthe present invention are configured to efficiently deliver the FSP,typically in the form of a frozen mist, from an extracorporeal locationinto a generally normo-thermic (i.e. approximately 37° C.) and highrelative humidity environment of a patient's lungs.

The tubular device 12 delivers the breathing gas and the FSP directly tothe patient's P lungs. The tubular device 12 will be configured forintraoral placement through the patient's esophagus and trachea and willinclude a cuff 14 which can be inflated via an inflation tube 16 toisolate a distal end of the tubular device within a main bronchus MB ofthe patient in a manner conventional for endotracheal tubes. The tubulardevice 12 is shown as a single body or extrusion having at least twolumens terminating in separate distal ports 18 and 20 to separatelydeliver the breathing gas and the FSP, respectively, to the patient'slungs L. The distal ports 18 and 20 will typically but not necessarilybe axially or otherwise separated to inhibit flow back of the FSP intothe breathing lumen which can result in melting and re-freezing of theFSP which, in turn, can cause clogging of the breathing lumen. Usuallythe breathing gas port will be disposed upstream (toward the mouth M) inthe main bronchus MB to minimize any direct contamination. Also, as willbe described below, the frozen particles are preferably delivered onlyduring the patient's inhalation cycle so the risk of FSP entering theexhalation lumen during the patient's exhalation cycle is reduced. Inother embodiments as described below, the tubular device may include anFSP delivery conduit which is separate from a breathing gas deliveryconduit. The separate FSP delivery conduit and breathing gas deliveryconduit may be arranged coaxially, in parallel, with relative helicalwinds, or the like.

After the patient P has been intubated with the tubular device 12,breathing air will be provided in a conventional manner from aventilator or other breathing source 22. In addition, successive bolusesof FSP will be delivered from an FSP source 24 through a valve 26. Asshown, the valve 26 controls the FSP flow, but in other embodimentsdescribed below a separate “puff” valve will provide bursts of carriergas which entrains the FSP to mix with the breathing gas and deliver theFSP into the lungs. A controller 28 senses the temperature of thepatient's exhalation through a temperature sensor 30 located at anoutlet of the tubular device 12. A shown in subsequent embodiments,temperature sensor could alternatively or additionally be located at avariety of locations in the system and/or on the patient, e.g. near adistal end of the tubular device 12 so that the temperature beingmeasured is closer to the lungs. This sensor may be used in any of themonitoring and/or control protocols described hereinbelow. Thetemperature measured by the sensor 30 will typically be provided to thecontroller 28 by a lead 32 and may be display on the controller to allowa physician or other user to manually adjust the delivery of the iceparticles in order to control the patient's core body temperature.Alternatively, valve 26 may be controlled via a signal line 34 whichreceives an automatic control signal from the controller 28 as describedabove. The system may include other sensors to indicate increased fluidin the lungs and/or increased ventilation pressure, and the data fromthose sensors may optionally be delivered to the controller toautomatically reduce an amount of FSP delivered if needed.

Usually, the ice or other FSP will be delivered during only a portion ofthe inhalation cycle. For example, as shown in FIG. 2 inhalation orventilation pressure P of the patient may be monitored, for example byusing a pressure sensor measuring the output pressure of the ventilator22, as shown at the top of FIG. 2. The pressure will typically be a sinewave 80 with a minimum occurring between successiveinhalations/ventilations. As shown in a second graph from the top ofFIG. 2, the FSP may be delivered in a series of bursts or puffs 82coming usually in the middle of the inhalation/ventilation cycle. Thenumber of bursts or puffs and amount of ice in each individual burst orpuff may be varied and the greater the number and/or volume of each puffwill, of course, translate into greater cooling of the patient.

While use of the puffs is desirable since it helps prevent clogging ofthe ice delivery components of the system it is not necessary. Thefrozen particles may alternatively be delivered in a single spike 86where the amount of frozen particles in the spike may be varied bycontrolling either the duration or the rate of the spike as shown insolid line and broken line, respectively. Similarly, the burst need notbe in the form of a square wave but could also have a time-varyingprofile as shown at the bottom of FIG. 2. Again, the duration or rate ofthe delivery will determine the total amount of frozen particlesdelivered in any given spike or release.

Patient Delivery System The frozen saline or other aqueous particles(FSP) are delivered by intubating the patient with the tubular device 12which includes a Patient Interface Tube (PIT) that is connected to theFSP reservoir 24 or other source. The PIT can have multipleconfigurations and can be heated, cooled or be free from activetemperature control. The PIT could have the heating/cooling element onlyin the internal part of the tube, only external part or both. It couldalso have a separated insulating layer at the outside. Theseconfigurations have advantages and applications in different situations.In order to function properly, the tube must remain unclogged during theoperation. Optionally, the tube may be polished and or have a layer ofhydrophobic or hydrophilic material coat its internal surface.

The PIT is the distal most component of the system through which the FSPpasses before coming in direct contact with the patient. The primaryfunction of the PIT is to allow the FSP (which may be aerosolized as dryparticles, aerosolized as wet particles, in the form of a slush, orotherwise) to freely flow from the FSP reservoir or other source,through the patient's trachea, and into the patient's lungs. The PIT iscarefully designed to inhibit or prevent blockage from frozen saline(occlusion of the flow lumen), unintended loss of ventilator tidalvolume, or other adverse interaction between the patient, the frozensaline, and/or other components of the system.

The PIT may have a variety of specific designs and may be combined withbreathing or ventilation tubes in a variety of configurations including:

Design 1: Actively Cooled PIT—utilizes cooled air to remove heat(thermal loads) from the device.

Design 2: Actively Warmed PIT—utilizes a NiCr wire or other heatingelement to apply heat (induce thermal loads) on the device.

Design 3: Multi-Lumen Polymeric PIT—designed for separate (independent)FSP delivery and breathing channels in a single, integrated tube andwhich may be actively cooled or actively warmed.

Design 4: Combined PIT-Ventilator Tube having Separable Components.

Design 1: Actively Cooled Patient Interface Tube. An actively cooled PITuses refrigerated breathing air or other gas (cooled by use of liquidnitrogen, liquid argon, liquid oxygen, thermoelectric, compressionrefrigeration, or other cooling methods) to reduce the temperature ofthe internal surface (diameter) of the frozen saline delivery lumen toor below 0° C. The temperature of the delivery tube is maintained below0° C. in order to prevent melting of FSP. The cold temperature of thePIT ensures that the FSP remains frozen in the PIT and preventsocclusion of the PIT lumen due to melting and refreezing of the FSP. ThePIT will usually be insulated on the outside in order to inhibitexcessive cooling of the trachea and prevent tissue damage.

As shown in FIG. 3, a PIT 100 can be designed to provide (1) frozensaline delivery, (2) an annular cooling space, and (3) a temperaturemonitoring system. A coolant, such as refrigerated air or gas (whichcould be the same as the breathing gas) is circulated through theannular cooling space 104 disposed coaxially about an FSP deliveryconduit 102. The temperature of the FSP delivery lumen can be monitoredwith one or more temperature sensors 106 and can be precisely controlledby metering the flow rate of the coolant through the annular coolingspace and/or by controlling the temperature of the coolant entering theannular cooling space. The PIT 100 will be insulated to prevent damageto the patient's trachea and can be constructed of metallic or polymericmaterials. Furthermore, upon exiting the annular cooling space, therefrigerated air may be utilized for cooling other components requiredfor the procedure or experiment. The temperature monitoring sensors 106may be thermocouples, thermistors, RTD's, or the like and may be placedalong the length of the FSP delivery conduit 102, usually along an innersurface thereof, at pre-selected intervals or locations to provide fortemperature monitoring and/or active, feedback control. The FSP aredelivered through an FSP delivery lumen 110 in the FSP delivery conduit102, and an insulating layer 108 will usually be provided over theexterior of the FSP delivery conduit 102 to protect the patient'strachea and esophagus from the low temperature of the annular coolingspace 104.

Design 2: Actively Heated Patient Interface Tube An actively heated PITuses a heater, such as a resistive wire heater (nickel-chrome alloy(NiCr), Alloy 52, or the like) to increase the temperature of at least aportion the FSP delivery lumen of the PIT to above 0° C. Withoutheating, passage of the FSP's through the lumen causes the tube wall ofthe PIT to cool. As the tube cools below 0° C. (freezing), the FSP'swill begin to melt in the delivery channel. Some of the liquid canrefreeze and agglomerate to partially or fully occlude the deliverylumen. By heating the tube wall above 0° C. (freezing), a liquidboundary layer is created that allows the FSP to “slide” easily throughthe tube. The temperature of the tube wall can be selected based on thedose or amount of the FSP being delivered. The PIT wall can be heated ina variety of ways, typically by wrapping a resistive coil around thetube and heating it with electrical current. Alternatively, the PIT wallcould be heated by supplying hot fluid (air, liquid) in a closed circuitaround the tube similar or identical to the design of FIG. 3.

An exemplary actively heated PIT 150 is illustrated in FIG. 4 andincludes an heating element, such as a heating coil 152, wrapped over anexterior surface of an FSP delivery conduit 154. An insulating layer 156covers the heating coil 152 as well as the remaining exterior surface ofthe FSP delivery conduit 154, and FSP are delivered through a centrallumen 158 of the FSP delivery conduit 154. Temperature monitoring may beprovided by one or more temperature sensors 160, particularly having atleast one sensor near a distal tip of the PIT to monitor temperature inthe patient's lung. The heating coil 152 and/or other heating elementsmay be wrapped around and/or potted into the PIT material. Connectors162 and 164 are provided for one or more temperature sensors.

Current or other energy is circulated through the heating elements,typically using a direct current (DC) power supply. The temperature ofthe FSP delivery lumen 158 can be precisely controlled by adjusting thelevel of voltage delivered to the heating coil 156 or other electricalheating elements, typically by using a variable voltage power supply,voltage divider, or the like. Alternatively or additionally, thetemperature in the FSP delivery lumen 158 may be maintained by on-offcontrol often using a controller-driven pulse width modulation (PWM)driver.

Design 3: Multi-Lumen Polymeric Patient Interface Tube. The PIT may beformed as an integrated unit to provide both breathing gas delivery andFSP delivery in a single device having at least two isolated lumens.Such integrated PIT-ventilator tube embodiments may be actively heated,actively cooled, or both actively heated and actively cooled to ensurethe FSP delivery lumen remains at the proper temperature for frozensaline delivery (as noted above) and that the breathing gas is deliveredat a desired temperature as well.

An exemplary multi-lumen integrated ventilator tube-PIT 200 is shown inFIGS. 5 and 5A and includes a polymeric body 202 similar in design anddimensions to a conventional endotracheal tube. The PIT body 202 isusually formed as a triangular extrusion, as shown in FIG. 5A, whichfacilitates passage through the larynx to the lungs. The larynx whichholds the patient's vocal cords has a generally triangular peripherywhen expanded and the portion if the body 202 which must pass throughthe larynx may have a periphery similar in size and shape so that theinternal area of the body available for creation of the FSP lumen, theventilator (breathing gas) lumen, and any other lumens may be maximized.

The body 202 will typically have at least several lumens including onelumen 204 for ventilating the patient using a conventional mechanicalventilation machine and another lumen 206 for delivery of FSP during theinhalation cycle of the patient. The ventilation lumen 204 and the FSPlumen 206 will usually be isolated from each other over their entirelengths to limit mixing of the FSP with warm humid air during exhalationof the patient. Moisture in warm exhalation air can freeze on the wallsof the FSP lumen, and the warm air can also partially melt the FSP tocreate further free liquid in the FSP lumen. Liquid from both sourcescan re-freeze on the FSP lumen wall which in turn can clog the lumen andsignificantly reduce performance of the system.

Optionally, one or more internal walls or septums within a multi-lumenextruded PTI body may be formed to be repositioned in response tochanges in pressure differential across the wall or septum. As shown inFIG. 6, a PIT-ventilator tube 250 having an extruded polymeric body 252can have an FSP delivery lumen 254 and a ventilation lumen 256 separatedand isolated by a movable septum 258. During inhalation, when thebreathing gas pressure is less than the FSP delivery pressure, theseptum 258 will shift to create a larger cross-section area for the FSPdelivery lumen 254, as shown in full line. Conversely, during exhalationwhen no FSP are being delivered, the exhalation pressure will begreater, shifting the position of the septum 258 to maximize the area ofthe ventilation lumen 256 which will reduce back pressure.

Referring again to FIGS. 5 and 5A, ventilator tidal volumes aredelivered through the ventilator lumen 204 while FSP is deliveredthrough the FSP lumen 206. In the particular embodiment of FIGS. 5 and5A, the cross-sectional (hydraulic) diameter of the breathing lumen maybe approximately equivalent to that of a 7 mm ETT, while the frozensaline delivery lumen has a relative size as shown. Temperaturemanagement features similar to those described for the actively cooledPIT (FIG. 3) and for the actively heated PIT (FIG. 4) may be used in theintegrated ventilator-PIT embodiments as well. The body 202 may includea thermal management lumen for routing heating wires around or adjacentto the FSP lumen 206, e.g. cooling or heating actuators could be used inparallel or independently to maintain the required temperatures for thebreathing lumen and frozen saline delivery lumen. The temperature of theventilator-PIT 200 may be controlled based on feedback from temperaturemonitoring devices (thermocouples, RTD, or otherwise) placed along thelength of the PIT at known intervals or locations. One or moreaspiration lumens 208 and 210 may also be provided to allow theventilator-PIT to aspirate excess water which accumulates in the lung asthe FSP melt after release.

Design 4: Combined PIT-Ventilator Tube having Separable Components.Referring to FIGS. 7 and 8, a combined PIT-ventilator tube assembly 300includes PIT 302 and a separate ventilation tube 304 having a centrallumen 305 which is configured to co-axially receive the PIT 302 asdescribed and illustrated below.

The PIT 302 has a one-way valve 306 at its distal end 308, as best seenin FIG. 7A. The one-way valve 306 is typically a duck bill valve havinga pair of a opposed flaps 309 which open and close in response to thedifferential pressure existing across the valve in any moment in time.In particular, the flaps 309 of the valve will open, as shown in brokenline in FIG. 7A, in response to a relatively higher pressure within alumen 320 of the PIT, which will occur for example when dispersed FSPare delivered in a distal direction through the PIT, as will bedescribed in more detail below.

PIT 302 may further comprise an alignment stop 310 near its proximal end312. Additionally, one or more electrical leads 314 will be provided tosupply electrical current to the PIT in order to heat the PIT, typicallyusing internal coils or tracings 318, as best seen in thecross-sectional view of FIG. 7B, and to provide a lead to one or morethermocouples 316 placed along the PIT. For example, a thermocouple orother temperature sensor 316 may be placed near the distal end 308 ofthe PIT in order to measure temperature within the patient's lung duringuse of the system. Additionally or alternatively, the plurality ofthermocouples or other temperature sensors may be placed along thelength of the PIT in order to measure temperatures within the centrallumen 320 as FSP is delivered down the lumen in order to help controland inhibit melting and refreezing of the FSP which could result inclogging of the lumen. The one-way valve 306 will also help inhibitclogging of the lumen as it will prevent moist air from the lung toenter the FSP delivery lumen 320 during the patient's exhalation cycle.The heating coils or tracings 318 may also be used to inhibit read asfreezing of ice along the interior wall of the FSP delivery lumen 320 byperiodically or continuously heating the luminal wall which inhibits theinoculation and accumulation of ice along the lumen wall in a mannersimilar to a frost-free freezer.

The ventilator tube 304 typically includes an inflatable balloon or“cuff” 322 at or near a distal end 324 thereof. The inflatable cuff 322will be similar to a cuff on a conventional endotracheal tube and willbe inflatable to seal against the patient's bronchus after thePIT-ventilator tube assembly 300 has been introduced to the patient'slungs through the patient's trachea. The cuff 322 will serve both tocenter the distal end 308 of the PIT so that dispersion of the FSP inthe lung is maximized and to seal the lung distal to the cuff so thatventilation of the patient can be controlled to maximize the deliveryand dispersion of FSP synchronously with the patient's ventilation, aswill be described in more detail below.

The combined PIT-ventilator tube assembly 300 will further include aninflation tube 326 having a connection port 328 at a proximal endthereof. The port 328 will be configured for connection to a syringe 358(FIG. 9) or other conventional balloon inflation source. ThePIT-ventilator tube assembly 300 will further include a proximal fitting332 having a port 330 for connection to a ventilator for providinginhalation and exhalation of the patient and a second port 331 to permitco-axial insertion of the PIT through the lumen 305 in order to assemblethe combined PIT-ventilation tube 300, as best shown in FIG. 8.

Once PIT 302 is inserted into the lumen 305 of the ventilation tube 304,a breathing lumen 342 will be formed by the annular space or gap betweenan exterior surface of the PIT 302 and an interior luminal surface ofthe ventilation tube 304, as best seen in FIGS. 8A-8C. Thus, breathinggas entering through the port 330 of the fitting 332 will be able totravel distally through the annular lumen 342 and will be able to exitthrough an annular opening surrounding the distal end 308 of the PIT.Insertion of the PIT 302 into the lumen 305 of the ventilation tube 304is limited by alignment stop 310 on the PIT which engages a proximalsurface 331 of the proximal fitting 332 on the ventilation tube 304.

Referring now FIG. 7C, an aspiration lumen 336 may optionally be formedin the wall of the ventilation tube 304, typically by using a“double-wall” structure providing an annular lumen 336 extending fromthe distal end 324 of the ventilation tube to the proximal fitting 332which includes an aspiration port 340. Conveniently, a plurality ofaspiration ports 338 may be formed at the distal end of the tube topermit aspiration of liquids which might accumulate in the lungs as aresult of melting FSP or other causes.

Referring now to FIG. 9, the assembled PIT-ventilator tube assembly 300may be connected to an FSP generator and controller 350 as well as to aseparate ventilator 352. The ventilator 352 may be a conventionalventilator connected to the PIT by a connector tube 364 or, in alternateembodiments, may be incorporated into the FSP generator and controller350. In either case, the FSP generator and controller 350 will producethe FSP which are delivered to the FSP lumen 320 of the PIT 302 via aconnector tube 362. The connector tube will typically be insulated toinhibit heat loss from and melting of the FSP as they travel through theconnecting tube. Optionally, the connecting tube 362 may be cooled tofurther inhibit heat loss and melting. Additionally or alternatively, inother embodiments, the connecting tube 362 may include heating elementsin order to prevent refreezing of melted FSP onto an interior luminalwall of the connecting tube. The ventilator 364 will be connected to theventilation port 330 on the proximal fitting 332 of the ventilator tube304. A syringe 358 or other conventional inflator may be connected tothe inflation port 328 on the inflation tube 326 to permit selectiveinflation of the cuff 322 after the assembly 300 is positioned with thedistal 308 of the vent tube within the bronchus to immobilize the tube,isolate the bronchus to allow the cooling protocol to begin.

As best shown in the detailed view FIG. 9A, FSP are delivered throughthe PIT 302 during at least a portion of the inhalation cycle of thepatient. In particular, the FSP are delivered through the PIT 302,causing the one-way valve 306 to open and release FSP 356 through thevalve. Concurrently, the breathing gas will be released through theannular gap between the outer surface of the PIT and inner, luminalsurface of the vent tube 304, allowing the breathing gas 354 to encircleand carryforward the particles 356 deep into the patient's lungs.

Referring now to FIG. 10, the FSP generator and controller 350 willtypically comprises a plurality of individual components to generate andcontrol the number of individual FSP boluses delivered to any of the PITand ventilator tube assemblies described hereinbefore. The FSP generatorand controller 350 will also usually provide heating power to the PITand/or vent tube as well as cooling gasses to other portions of thesystem as needed and as described elsewhere herein. Typically, theventilator 352 will be a separate system component, often being acommercial unit which has been modified to be controlled in combinationwith the FSP generator. In particular, a pressure sensor 355 may beconnected to measure the output pressure of the ventilator 352 andprovide a pressure signal to the controller 370 of the FSP generator andcontroller 350. The pressure sensor 355 may be part of the commercialsystem or may be added to the commercial system. In either case, it willbe used to monitor the inhalation and exhalation cycles generated by theventilator. Typically, the controller 370 will also be electronicallyinterfaced with the ventilator 352 so that the operational parameters ofthe ventilator can be adjusted by the controller 370. In otherembodiments, the ventilator may be provided as part of the FSP generatorand control system itself so that all components of both the FSPgenerator and ventilator may be included in a single unit.

The FSP generator and controller 350 will include a gas source 372 toprovide pressurized gas for dispersing the FSP and delivering thedispersed FSP to the PIT. The gas source 372 will be non-toxic andtypically comprise a conventional breathing gas, such as air, oxygen,heliox, or any gas of the type which may be used in conventional patientventilation. The gas will typically be provided in a pressurized gasbottle, but use of a compressor for generating compressed air or otherbreathing gases will also be possible. Pressurized gas from the gassource 372 is delivered through a heat exchanger 374, typically a liquidnitrogen cooler, which lowers the temperature of the gas before it isused to disperse the FSP. At least most of the gas from the heatexchanger 374 will be delivered to a “puff” valve 376 and will be usedto disperse the FSP, but a side stream 377 can also be taken off toprovide for various other cooling functions within the system, forinstance cooling of the PIT illustrated in FIG. 3.

The puff valve 376 is controlled by controller 370 so that it will opento allow pressurized gas to flow during the patient's inhalation cyclein order to generate FSP for delivery to the patient during theinhalation cycle. Specifically, gas from the puff valve 376 flows intoan FSP dispersion unit 380, which is best described in connection withFIG. 11 below, and the resulting boluses of FSP will then usually flowinto a blocking valve 382 which forms part of a blocking and vent valveunit 386. The blocking valve 382 will be opened simultaneously with thepuff valve 376 and will be closed during the exhalation cycle of thepatient to inhibit backflow of exhalation gases into the PIT and otherportions of the cooling system.

A vent valve 384 which forms part of the blocking and vent valve unit386 serves a different purpose. The vent valve 384 will also be openedduring at least a portion of the inhalation cycle when FSP are beingdelivered in the flow of puff gases through the particular generator380. It has been found that full dispersion of the FSP requires arelatively high volume of dispersion gas. While the dispersion gases arenon-toxic, and will often be the same gas as the breathing gas deliveredby the ventilator, is undesirable that the dispersion gases form amajority of the tidal volume to be delivered to the patient during eachinhalation cycle. The vent valve allows a portion of the excessdispersion gases to be vented from the system. Once the FSP aredispersed in the puff of dispersion gases after having passed throughthe particle dispersion unit 380, it is possible to vent a significantportion of these “carrier” or dispersion gases from the flowing FSPstream. Thus, by providing a vent valve 384, typically in combinationwith a flow control orifice (not shown), a significant portion of thecarrier or dispersion gasses may be bled from the system before beingdelivered to the patient. Typically more than 50%, often more than 60%,and sometimes as much 80% of more of the dispersion gasses may bevented. In this way, the majority of breathing gas delivered to thepatient will come from the ventilator 352 which may be controlled tomaintain patient ventilation in a more normal manner and may also beused to deliver anesthetics, or for other therapeutic purposes. Thegasses leaving the blocking/vent valve unit 386 will then be deliveredto the PIT as shown in more detail hereinbelow.

Gasses from the ventilator 352 may also optionally be passed through aheat exchanger 375, which again will typically be a liquid nitrogen heatexchanger. The heat exchanger used for cooling the breathing gasses maybe the same as heat exchanger 374 use to cool the dispersion gasses. Theheat exchanger 375 is provided at the output of the ventilator, it ispreferred that a bypass 377 be provided for the exhalation gasses thatare being returned to the ventilator.

Referring now to FIG. 11, the particle dispersion unit 380 willtypically include an FSP hopper 400 which is usually maintained in acold environment such as in a liquid nitrogen cooler or thermoelectricor other refrigerator. A mixer 402 helps the FSP flow downward through achute 404 into a measuring receptacle 406 within a block or breech 408.The block 408 includes a transverse passage 410 which intersects thechute 404 so that FSP fall into the portion of the chute within thepassage 410 in a repeatable manner to provide a measured amount of FSPtherein. A bolt 412 having a hollow bore 414 is reciprocatably mountedso that an open distal end 14 may be advanced into the measuringreceptacle 406 to separate a measured portion of the FSP, as will bedescribed in more detail below. A proximal end 418 of the bolt 412 has aproximal fitting 420 which is connected to a flexible line 422 whichreceives the dispersion gas from the puff valve 376, seen in FIG. 10. Ataper tube 422 is connected to the downstream end of the passage 410 inthe block 408 so that FSP may be delivered to a line 426 which isconnected to the blocking/vent valve assembly 386, again as shown inFIG. 10.

Referring now to FIGS. 12A-12D, the particle dispersion unit 380 isshown at the beginning of its measurement and dispersion cycle in FIG.12A. The bolt 412 is distally advanced in the direction of arrow 428 sothat the open distal end 416 passes through and “cores” a portion of theFSP in the measuring receptacle 406.

After the bolt 412 has passed through the measuring receptacle 406,advancement of the bolt is terminated, and puff valve 376 is opened torelease a “puff” of dispersion gas through the line 422 and into thehollow bore 414 of the bolt 412 as shown by arrow 430 in FIG. 12C. Thedispersion gas expels the FSP which had been present in the bore 414 sothat a bolus 432 of the dispersed FSP is dispersed and advanced throughthe taper tube 424 and into the transfer tube 426 which leads to theblocking/vent valve assembly 386, as shown in FIG. 10.

As shown in FIG. 12D, after bolus 432 of the FSP has been delivered, thebolt 412 may be retracted to its initial position up stream of themeasuring receptacle 406, allowing additional FSP to fall by gravityinto the measuring receptacle. The particle dispersion unit 380 is thenready for the next cycle of bolus generation which will typically begenerated upon the next inhalation cycle of the patient by thecontroller 370. Other configurations for the particle dispersion unit380 may be found in provisional application No. 62/131,773, filed onMar. 11, 2015. Priority has been claimed from this provisionalapplication, and the entire content of this application has beenincorporated herein by reference.

Referring now to FIGS. 13A-13B, exemplary embodiments for theblocking/vent valve unit 386 will be described. Both the blocking valve382 and the vent valve 384 will typically be “pinch” valves includingopposed pinching elements 438 and 440, respectively. The dispersion line426 which receives the dispersed FSP from the particulate dispersionunit 380 and delivers the dispersed FSP in the direction of arrow 434will be a flexible tube so that the pinching elements 438 and 440 may beclosed over the tube to selectively close the lumens through the tubes,as shown in FIG. 13A, or open said lumens, as shown in FIG. 13B. Thevalves 382 and 384 will both be closed and during the exhalation cycleof the patient, helping inhibit backflow of the exhalation gassesthrough the PIT and any other portions of the system. When deliveringFSP into the inhalation gas, however, the valves 382 and 384 will beopened. Opening valve 382 permits the FSP to flow to the PIT whileopening of the vent valve 384 allows excess carrier gas to be ventedfrom the dispersed gas stream so that the amount of breathing gasdelivered to the patient from the dispersion gas stream is reducedrelative to the amount being delivered through the breathing gas streamfrom the ventilator. Details of the construction for alternativeembodiments for the blocking/vent valve unit are found in provisionalapplication No. 62/277,412 filed on Jan. 11, 2016, the full disclosurewhich has previously been incorporated here and by reference. Priorityhas been claimed to this provisional application.

In other aspects of the present invention, a multi-lumen PIT-ventilationtube will include features to manage the vocal cord region of the upperairway. Such embodiments may include an airway sealing balloon orbladder to seal the oral cavity, a dilation feature for holding open thevocal cord region to allow for the breathing tube to terminate above thevocal cords which enables the ability to ventilate the patient withouthaving to insert additional tubes through the vocal cord region.Additionally, at the distal end of the PIT-ventilation tube, a centeringfeature is deployed to maintain the frozen saline particle delivery tubecentrally within the trachea. Several other tubes are described toinsulate the cold tube from the airway tissue as well as features fordeploying and retracting the balloons, dilation and centering features.These embodiments solve the problem of being able to access the tracheathrough the vocal cord region which is geometrically constraining. Inparticular, fewer tubes are required to be placed beyond the vocal cordsfacilitating access to the trachea with the components required fordelivering FSP to the lungs.

Other embodiments reduce pressure on the vocal cords over long timeperiods. The FSP delivery tube in any of the configurations describedabove can have a short segment in the area of the epiglottis and vocalcord that is narrower than the upstream and/or downstream portion of thetube. Such a narrow segment will require increasing the upstreamventilation and frozen saline particle delivery pressures, but thosepressures will fall to normal downstream of the narrowing. In apreferred embodiment the cross section of the tubes will be triangularin shape to fit the space between the vocal cords.

Additionally, each of the embodiments described above may optionallyhave one or more secondary features. As previously illustrated, the PITmay include a duck-bill or similar pressure-responsive one-way valve atthe distal end of the FSP delivery tube in order to inhibit warm, humidair from entering the FSP delivery tube during the exhalation cycle ofthe patient. By allowing flow only in the inhalation direction, entry ofthe tracheal fluids in the FSP delivery lumen is prevented. If allowedto enter the FSP lumen, the fluids can freeze and partially or whollyocclude the flow of FSP thought the lumen. The duckbill valve isdesigned to prevent humidified air, bodily secretions, or otherundesired substances or fluids from entering the PIT from the distalend. The duckbill valve is typically formed from a polymeric materialand is placed at the distal exit of the frozen saline delivery lumen.

A centering/sealing balloon provides two functions. First, the ballooncan be inflated to force the PIT away from the tracheal wall, thusallowing the duckbill valve to freely move and actuate. Second, theballoon can seal the trachea so that automated ventilation may beperformed through a combined ventilation-PIT tube assembly.

Additional system features include hydrophobic and/or hydrophiliccoating on the inside of the delivery tube as well as the frozen salineparticle transfer tubes to help in the FSP transport by facilitatingsmooth passage and reduce clogging. In addition to coating, the air usedto carry the frozen saline particles is generally very cold and dry and,thus, can build up electrostatic charge in the frozen saline particlereservoir, transfer tubes, and patient interface tube. Consequently, airionization can be employed to modify the charge carried by the frozensaline particles and the carrying air to help reduce static build up andpotentially improve the flow of the frozen saline particles through thesystem and reduce the potential for clogging.

The foregoing description of various embodiments of the invention hasbeen presented for purposes of illustration and description. It is notintended to limit the invention to the precise forms disclosed. Manymodifications, variations and refinements will be apparent topractitioners skilled in the art. For example, embodiments of the devicecan be sized and otherwise adapted for various pediatric applications aswell as various veterinary applications. Also those skilled in the artwill recognize, or be able to ascertain using no more than routineexperimentation, numerous equivalents to the specific devices andmethods described herein. Such equivalents are considered to be withinthe scope of the present invention and are covered by the appendedclaims below. Elements, characteristics, or acts from one embodiment canbe readily recombined or substituted with one or more elements,characteristics or acts from other embodiments to form numerousadditional embodiments within the scope of the invention. Moreover,elements that are shown or described as being combined with otherelements, can, in various embodiments, exist as standalone elements.Hence, the scope of the present invention is not limited to thespecifics of the described embodiments, but is instead limited solely bythe appended claims.

What is claimed is:
 1. A system for lowering a core body temperature ofa patient to be used in combination with an external ventilatorconfigured to deliver a breathing gas to a bronchus of a lung of thepatient, said system comprising: a tubular device configured foradvancement through the patient's trachea to the bronchus, said tubulardevice having a breathing lumen and a frozen particle (FSP) lumenisolated from the breathing lumen; an external FSP source configured todeliver FSP to the FSP lumen of the tubular device; and a controllerconfigured to adjust the amount or rate of delivery of FSP from theexternal FSP source through the at least one FSP lumen, whereby a targetcore temperature of the patient can be achieved and maintained byadjusting the amount or rate of delivery of the FSP; and means forinhibiting clogging of the FSP lumen resulting from melting andrefreezing of the FSP in the lumen.
 2. A system as in claim 1, whereinthe means for inhibiting clogging of the FSP lumen comprises a heaterconfigured to heat the FSP lumen to inhibit clogging of the FSP lumenresulting from melting and refreezing of the FSP in the lumen.
 3. Asystem as in claim 2, wherein the heater comprises electrical tracingpositioned over at least a portion of the FSP lumen.
 4. A system as inclaim 1, wherein the means for inhibiting clogging of the FSP lumencomprises a cooler configured to cool the FSP lumen to inhibit cloggingof the FSP lumen resulting from melting and refreezing of the FSP in thelumen.
 5. A system as in claim 1, further comprising a sensor configuredto measure a temperature of an exhaled gas or body temperature, whereinthe controller adjusts the amount or rate of delivery of FSP through theFSP lumen in response to changes in the measured temperature.
 6. Asystem as in claim 1, wherein the controller is configured toautomatically control the delivery amount or rate of FSP in response tothe measured temperature according to a feedback control algorithm.
 7. Asystem as in claim 4, wherein the controller is configured to allow auser to manually control the delivery amount or rate of FSP delivery inresponse to the measured temperature.
 8. A system as in claim 1, whereinthe external FSP source comprises a means for providing a bolus of FSPand flowing a volume of carrier gas through the bolus to entrain the FSPin the flowing carrier gas to produce an FSP-entrained flowing carriergas stream.
 9. A system as in claim 8, wherein the external FSP sourcefurther comprises a means for venting a portion of the carrier gas fromthe FSP-entrained flowing carrier gas stream to produce a gas reducedFSP-entrained flowing carrier gas stream, wherein said gas reducedFSP-entrained flowing carrier gas stream is delivered to the FSP lumen.10. A system as in claim 9, wherein the controller is configured tocontrol venting of the carrier gas to produce a tidal volume of totalbreathing gas delivered to the patient in the range from 150 ml to 1000ml per inhalation cycle.
 11. A system as in claim 10, wherein thecontroller is configured to vent at least 50% of the gas originallypresent in the FSP-entrained flowing carrier gas stream to produce thegas reduced FSP-entrained flowing carrier gas stream.